The regulation of endogenous retinoic acid level through CYP26B1 is required for elevation of palatal shelves
Article first published online: 25 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 241, Issue 11, pages 1744–1756, November 2012
How to Cite
Okano, J., Kimura, W., Papaionnou, V. E., Miura, N., Yamada, G., Shiota, K. and Sakai, Y. (2012), The regulation of endogenous retinoic acid level through CYP26B1 is required for elevation of palatal shelves. Dev. Dyn., 241: 1744–1756. doi: 10.1002/dvdy.23862
- Issue published online: 17 OCT 2012
- Article first published online: 25 SEP 2012
- Accepted manuscript online: 12 SEP 2012 02:59PM EST
- Manuscript Accepted: 23 AUG 2012
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health
- retinoic acid;
- cleft palate;
Background: In previous studies, we investigated the effects of excess retinoic acid (RA) during palatogenesis by RA administration to pregnant mice. In the present study, we deleted Cyp26b1, one of the RA-degrading enzymes, to further study the effects of excess RA in the normal developing palate and to understand how endogenous levels of RA are regulated. Results: Excess RA, due to the absence of Cyp26b1, targets cells in the bend region of the palatal shelves and inhibits their horizontal elevation, leading to cleft palate. An organ culture of Cyp26b1−/− palatal shelves after tongue removal did not rescue the impaired elevation of the palatal shelves. The expression of Fgf10, Bmp2, and Tbx1, important molecules in palatal development, was down-regulated. Cell proliferation was decreased in the bend region of palatal shelves. Tongue muscles were hypoplastic and/or missing in Cyp26b1−/− mice. Conclusions: We demonstrated that CYP26B1 is essential during palatogenesis. Excess RA due to the lack of Cyp26b1 suppresses the expression of key regulators of palate development in the bend region, resulting in a failure in the horizontal elevation of the palatal shelves. The regulation of RA signaling through CYP26B1 is also necessary for the development of tongue musculature and for tongue depression. Developmental Dynamics 241:1744–1756, 2012. © 2012 Wiley Periodicals, Inc.